Comparative metabolism of phenobarbitone in the rat (CFE) and mouse (CF1)

The fate of orally administered [ 14C]phenobarbitone (40 mg/kg) was studied comparatively in CFE rats and CF1 mice. Metabolism and elimination were rapid. Hydroxylation was more complete in rats than in mice but the major metabolite in both species was p-hydroxyphenobarbitone, which was excreted mostly in the urine in both free and conjugated form. Unmetabolized phenobarbitone was excreted in the urine of both rat and mouse. Two minor metabolites appeared to be common to both species. The effect of pretreatment with non-radioactive phenobarbitone on the metabolism of [ 14C]phenobarbitone was minimal in the rat but afforded a twofold increase in p-hydroxylation in the mouse ( in vivo). Despite the good yield of p-hydroxyphenobarbitone in the intact rat, [ 14C]phenobarbitone was not metabolized by liver-microsomal preparations from either untreated or phenobarbitone-induced rats.